Chemokines are a family of chemoattractant, proinflammatory cytokines which are essential for homeostasis and activation of the immune system. They direct migration of immune cells into sites of inflammation and infection. Chemokines bind to specific cell surface receptors belonging to the family of 7-transmembrane domain, G protein-coupled receptors (GPCRs).
CCR6 is a chemokine receptor belonging to Class A of the GPCR superfamily and it is expressed on human dendritic cells, memory T cells and on B cells (Zaballos et al., (1996) Biochem & Biophys Res Com, 227: 846-853; Greaves et al., (1997) J Exp Med, 186: 837-844; Power et al., (1997) J Exp Med 186: 825-835; Liao et al., (1999) J Immunol 162: 186-94). The only known ligand for CCR6 is the chemokine CCL20 also known as MIP-3α, LARC or exodus (Rossi et al., (1997) J Immunol 158: 1033-1036). The CCR6 receptor was first cloned from human genomic DNA as an orphan receptor (Zaballos et al., supra). Northern blot analysis has revealed that CCR6 is expressed mainly in spleen, lymph nodes, thymus, appendix, and PBMCs among various human tissues (Baba et al., (1997) J Biol Chem, 272: 14893-14898). Among various leukocyte subsets, CCR6 mRNA has been detected in lymphocytes (CD4+ and CD8+ T cells and B cells) but not in natural killer cells, monocytes, or granulocytes (Baba et al., supra). The chemokine ligand/receptor pairing CCL20/CCR6 is interesting because these molecules display characteristics of both homeostatic and activation functions and these dual characteristics suggest a role for CCR6 in the priming and effector phases of the immune response.
Due to its expression on Th17 cells (Romagnani S et al., (2009) Mol Immunol 47: 3-7), CCR6 is involved in a plethora of autoimmune and inflammatory diseases, for example, atopic dermatitis, contact dermatitis, mycosis fungoides, psoriasis, chronic hepatitis, periodontal disease, HPV, IBD, rheumatoid arthritis, allergic asthma, COPD, delayed-type hypersensitivity, B-cell malignancies, breast adenocarcinoma, hepatocellular carcinoma, pancreatic adenocarcinoma, thyroid papillary carcinoma and glioblastoma.
Workers have generated antibodies against CCR6 using a variety of methods for instance using Phage Display WO2013184218 (MSM PROTEIN TECHNOLOGIES). Anti-CCR6 antibodies have also been generated using conventional immunisation methods WO2001017558A3 (SCHERING CORPORATION). All such prior art antibodies do not have the properties necessary to be suitable as therapeutic antibodies. That is although some or all of these antibodies have binding affinity for human CCR6, they do not have or have not been demonstrated to have the ability to modulate the activity of the human CCR6 receptor, for instance the ability to prevent CCR6 dependent cell migration. Such prior art antibodies have also not been shown to be suitable for use as diagnostic antibodies, as they are not CCR6 specific.
Therefore there remains a need in the art for compositions that can be used in the treatment and diagnosis of diverse immune and inflammatory diseases and disorders.